The principal objective of this research is to measure the intranuclear distribution and macromolecular associations of specific DNA molecules in the nucleus of normal and malignant mammalian cells as the cells change in metabolic activity and growth. The basic approach is to analyze the genomes of normal diploid, heteroploid and cancerous cells of human, monkey and mouse origin under controlled conditions of cell culture. These varying conditions include active growth, contact inhibition and stimulation to differentiated function. The properties, amounts, and redistribution of highly repetitive, intermediate, and unique DNA sequences are followed in subnuclear fractions as the cells undergo in vivo physiological changes. An analysis will be made of any special proteins that may be uniquely associated with the most highly repetitive (satellite) DNA's which acts as a repressor of their transcription. The direct isolation and characterization of the macromolecules will help to clarify the role of the many specific types of DNA and their intermolecular associations in the mammalian nucleus and lead to an understanding of their possible function in the regulation of normal and malignant cell growth.